A Rubik's cube as a reconfigurable microfluidic system is presented in this work. Composed of physically interlocking microfluidic blocks, the microfluidic cube enables the on-site design and configuration of custom microfluidics by twisting the faces of the cube. The reconfiguration of the microfluidics could be done by solving an ordinary Rubik's cube with the help of Rubik's cube algorithms and computer programs. An O-ring-aided strategy is used to enable self-sealing and the automatic alignment of the microfluidic cube blocks. Owing to the interlocking mechanics of cube blocks, the proposed microfluidic cube exhibits good reconfigurability and robustness in versatile applications and proves to be a promising candidate for the rapid deployment of microfluidic systems in resource-limited settings.